Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway
Colon cancer cell chemosensitisation by fish oil emulsion involves apoptotic mitochondria pathway
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DOI：
10.1017/s000711451200308x
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发表时间：
2013-04-14
影响因子：
3.6
通讯作者：
Pichard, Claude
中科院分区：
文献类型：
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作者：
Granci, Virginie;Cai, Fang;Pichard, Claude
辅助使用具有抗肿瘤特性的安全化合物已被提出以改善癌症化疗结果。研究富含n-3多不饱和脂肪酸的鱼油乳剂(FOE)与标准化疗药物5-氟尿嘧啶(5-FU)、奥沙利铂(OX)和伊立替康(IRI)对两种不同遗传背景的人结肠腺癌细胞的作用。HT-29(Bax(+/+))和LS174T(Bax(-/-))细胞分别与1 mU M-5-FU、1 mU M-OX或10 mU M-IRI和/或相当于24 mU M-EPA和20.5 mU M-DHA的稀释液共同作用24-72 h。以大豆油乳剂(SOE)为等能、等脂对照。用细胞毒比色法、Annexin V流式细胞术和4‘，6’-二氨基-2-苯基吲哚染色分别检测细胞存活率、细胞凋亡率和细胞核形态变化。用阳离子荧光探针检测线粒体功能障碍，Western印迹法检测线粒体凋亡相关蛋白的表达。与SOE相比，FOE可显著增强5-FU、OX或IRI对HT-29细胞的促凋亡和细胞毒作用，但对LS174T细胞的促凋亡和细胞毒作用不明显(双向方差分析，P<；0.01)。这些结果被HT-29细胞中的凋亡体的形成所证实。5-FU或IRI与FOE联合作用后，线粒体膜去极化显著增加，但对LS174T细胞无明显影响(P<；0.05)。FOE与标准药物5-FU、OX和IRI联合给药，可能是通过Bax依赖的线粒体途径提高化疗方案疗效的一个很好的替代方案。
Adjuvant use of safe compounds with anti-tumour properties has been proposed to improve cancer chemotherapy outcome. We aimed to investigate the effects of fish oil emulsion (FOE) rich in n-3 PUFA with the standard chemotherapeutic agents 5-fluorouracil (5-FU), oxaliplatin (OX) or irinotecan (IRI) on two human colorectal adenocarcinoma cells with different genetic backgrounds. The HT-29 (Bax(+/+)) and LS174T (Bax(-/-)) cells were co-treated for 24-72 h with 1 mu M-5-FU, 1 mu M-OX or 10 mu M-IRI and/or FOE dilution corresponding to 24 mu M-EPA and 20.5 mu M-DHA. Soyabean oil emulsion (SOE) was used as isoenergetic and isolipid control. Cell viability, apoptosis and nuclear morphological changes were evaluated by cytotoxic colorimetric assay, flow cytometry analysis with annexin V and 4',6'-diamidino-2-phenylindole staining, respectively. A cationic fluorescent probe was used to evaluate mitochondrial dysfunction, and protein expression involved in mitochondrial apoptosis was determined by Western blot. In contrast to SOE, co-treatment with FOE enhanced significantly the pro-apoptotic and cytotoxic effects of 5-FU, OX or IRI in HT-29 but not in LS174T cells (two-way ANOVA, P < 0.01). These results were confirmed by the formation of apoptotic bodies in HT-29 cells. A significant increase in mitochondrial membrane depolarisation was observed after the combination of 5-FU or IRI with FOE in HT-29 but not in LS174T cells (P < 0.05). Co-administration of FOE with the standard agents, 5-FU, OX and IRI, could be a good alternative to increase the efficacy of chemotherapeutic protocols through a Bax-dependent mitochondrial pathway.